One hundred eighty-two African-Americans (74 Men, 108 Women) have participated. This cohort is known as TARA for: Triglyceride and Cardiovascular Risk in African Americans. In addition 90 Black Africans (52 Men, 38 Women) living in the United States have enrolled. This cohort is known as BART for: Black Africans and Cardiovascular Risk from Triglyceride. The sample of African Americans participating can be considered representative of the African American population of the United States because the prevalence of obesity (43%), pre-diabetes (22%) and hypertension (21%) is similar to NHANES data. NHANES stands for National Health and Nutrition Examination and is a nationwide survey with thousands of participants. However,there is no national data on the metabolic and diabetic health of Black Africans living in the United States (BA-USA). We have made the finding that the overall rate of pre-diabetes and hypertension is almost twice as high in BA-USA men than African American men. Furthermore, the rate of undiagnosed diabetes in self-identified healthy individuals was 3% in BA-USA vs 0% in African American men. In contrast the rate of hypertension, diabetes and pre-diabetes are similar in BA-USA women and African American women. Identifying the reasons for this less healthy metabolic profile of BA-USA men compared to African American men has become a major focus of research in this protocol. To improve and then maintain good health in BA-USA men, it is essential to understand why pre-diabetes, diabetes and hypertension is occurring in BA-USA men even though BA-USA men are less obese, more likely to be non-smokers, more likely to be married and have similar educational levels and income as African American men. The body size of the African American and BA-USA participants range from lean to obese. The mean body mass index of participants is 30.6 kg/m2 for African Americans but only 26.4 kg/m2 in BA-USA. Body mass index is a mathematical method used to correct weight for height. Due to the broad range of body mass index in the participants it is possible to make conclusions about the relationship of body size to insulin resistance. It is insulin resistance that is a major factor in the development of diabetes, heart disease and hypertension. So to have a way to predict insulin resistance based on body size is essential. A key way to assess body size is by waist circumference as waist circumference is a measure of central obesity. We have found in African American men that a waist circumference of 102 cm in men predicts both insulin resistance and obesity. This in agreement with the National Cholesterol Education Program values for whites. However, in African American women we found that a waist circumference of 98 cm predicted both insulin resistance and obesity. Based on investigations in white women the National Cholesterol Education Program recommends that a waist circumference threshold of 88 cm be used. Therefore our work demonstrates the need for ethnic-specific modifications of guidelines in women. In addition, we have now expanded our study of total and central obesity to include both African American women as well as BA-USA women. Plus we are in the process of comparing and combining our results with investigators from South Africa and through a collaboration with Dr. Rotimi (NHGRI) with West African women living in Nigeria and Ghana. Therefore our work should directly lead to the first investigations which simultaneously study these issues in women of African descent worldwide. Elevated TG and low HDL are considered lipid hallmarks of insulin resistance. However while elevated TG is a marker of insulin resistance in whites, we have shown that TG is not a marker of insulin resistance in African Americans. The investigation of the relationship of TG to insulin resistance is such an important component of this research program, that the cohort of African Americans pparticipating in this protocol are known as TARA which, as stated above, stands for Triglyceride and Cardiovascular Risk in African Americans. Results from TARA were so impressive that the hypothesis that TG was not a marker of insulin resistance in African Americans was tested in NHANES data from 1999-2001. In this nationwide data set of whites, African Americans and Mexican Americans, the fact that TG was not a marker of insulin resistance was confirmed. However, TG was a marker of insulin resistance in whites and Mexican Americans. Again this demonstrates that to detect early disease in African Americans there is a need for ethnic-specific guidelines. More recently the TG/HDL ratio at a level of >3.0 has been suggested to be a marker of insulin resistance. This is well established in whites. But we have shown using TARA data, that this did not work in African Americans. Very recently, we were asked to prove if this was the case using the much larger data set of the Jackson Heart Study, a cohort of 5000 African Americans living in Jackson, Mississippi. This larger dataset was a sufficient size to examine men and women separately. We found, and this work is now in press, that the ratio at the ethnic-specific level of 2.5 actually worked in African Aemrican men to predict insulin resistance, but did not work in African American women. In fact, in women the ratio would give incorrect results >50% of the time. Therefore to identify and prevent diseases related to insulin resistance in African American women, we have to identify which tests do work. Best health will only be achieved with accurate and correct early screening. In the next phase of this work, we plan to test the TG/HDL ratio in BA-USA and black South African women as well West African women. This would be a second collaboration with the groups we brought together to study guidelines for the WC of risk in women of African descent. Another key component of this research program is to develop an index of free fatty acid sensitivity to insulin. Free fatty acids are the building blocks used by the body to build TG. There are three fatty acids in each TG particle. In this initiative we are working with mathematicians. The modeling is underway. Due to the multiplicity of hormones that affect free fatty acid levels as well as the wide range of biological variation in free fatty acids, achieving a model of the effect of insulin on free fatty acids is a great challenge. Nonetheless, the complex multicompartment modeling is underway. Our preliminary findings are that the rate of clearance of free fatty acids from the circulation is higher in black women than white women. If this is confirmed in our future studies we would have made a big step forward in understanding race and ethnic differences in TG metabolism. In summary, our work is dedicated to preventing cardiovascular disease and diabetes in people of African descent worldwide by achieving a better understanding the ethnic-specific risk factors.